Coated medical devices and methods of making and using same

ABSTRACT

Coating methods and related devices are provided. Such devices can include stents. For example, the device can comprise a sidewall and a plurality of pores in the sidewall that are sized to inhibit flow of blood through the sidewall into an aneurysm to a degree sufficient to lead to thrombosis and healing of the aneurysm when the tubular member is positioned in a blood vessel and adjacent to the aneurysm. The device can also comprise an anti-thrombogenic coating distributed over at least a portion of the device such that the pores are substantially free of webs formed by the coating.

RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 13/844,577, filed Mar. 15, 2013, titled COATED MEDICAL DEVICESAND METHODS OF MAKING AND USING SAME, the entire contents of which areincorporated by reference herein and made a part of this specification.

BACKGROUND

Walls of the vasculature, particularly arterial walls, may develop areasof pathological dilatation called aneurysms. As is well known, aneurysmshave thin, weak walls that are prone to rupturing. Aneurysms can be theresult of the vessel wall being weakened by disease, injury, or acongenital abnormality. Aneurysms could be found in different parts ofthe body, and the most common are abdominal aortic aneurysms and brainor cerebral aneurysms in the neurovasculature. When the weakened wall ofan aneurysm ruptures, it can result in death, especially if it is acerebral aneurysm that ruptures.

Aneurysms are generally treated by excluding the weakened part of thevessel from the arterial circulation. For treating a cerebral aneurysm,such exclusion is done in many ways including: (i) surgical clipping,where a metal clip is secured around the base of the aneurysm; (ii)packing the aneurysm with small, flexible wire coils (micro-coils);(iii) using embolic materials to “fill” an aneurysm; (iv) usingdetachable balloons or coils to occlude the parent vessel that suppliesthe aneurysm; and (v) intravascular stenting.

Intravascular stents are well known in the medical arts for thetreatment of vascular stenoses or aneurysms. Stents are prostheses thatexpand radially or otherwise within a vessel or lumen to provide therapyor support against blockage of the vessel. Methods for delivering theseintravascular stents are also well known.

Various other implantable devices are used in surgical procedures.Often, these stents and other devices are coated with a coating materialin order to achieve a desired therapeutic or other effect.

SUMMARY

In accordance with some embodiments disclosed herein, a heat-treateddevice (e.g., stent) is provided that comprises an even coating that issubstantially free of imperfections, such as lumps, fibers, webs, and/orother obstructions in the pores of the device. Such a device can bebraided and/or have a flow diverting section.

Aspects of some embodiments disclosed herein recognize the existence ofsignificant challenges in manufacturing a flow diverting device, such asa stent, that has a coating evenly applied over its surface. Hitherto,no process or device known to the Applicants has been developed thatprovides a device, such as a braided stent, with a coating that isevenly distributed over its surface, e.g., a coating that is devoid ofimperfections, such as lumps, webs, fibers, or other obstructions in thepores of the stent.

Some embodiments disclosed herein provide a device with at least oneflow diverting section that is coated and substantially free of webbingor that has a substantially uniform coating. Some embodiments relate tocoating processes by which a device (e.g., a braided stent) can receivean even, generally imperfection-free coating. Additionally, someembodiments relate to methods of treatment using such coated devices(e.g., braided stents). Furthermore, some embodiments relate to one ormore of the various advantageous features of the coated devices (e.g.,braided stents).

For example, in some embodiments a medical device is provided fortreating an aneurysm. The device can comprise a tubular body comprisinga plurality of braided filaments and configured to be implanted in ablood vessel. The body can be expandable to an expanded state fortreatment of the aneurysm. The body can have a first section forspanning the neck of the aneurysm and a plurality of pores locatedbetween the filaments. The pores in the first section can have a firstaverage pore size of less than about 500 microns when the body is in theexpanded state. The first section can have a substantially completecoating, comprising a coating material, over the filaments. Further, thefirst section can be substantially free of webs formed between thebraided filaments by the coating material.

The first section can comprise a length less than an entire length ofthe tube. The coating material on the first section can be generallyuniform over the device or filaments. The coating can comprise anantithrombogenic material.

The medical device can further comprise a second section having aplurality of pores having a second average pore size greater than thefirst average pore size.

Further, some embodiments can provide a delivery system for treating ananeurysm. The system can comprise a microcatheter configured to beimplanted into a blood vessel, a core assembly, extending within themicrocatheter, having a distal segment, and the device extending alongthe core assembly distal segment.

Furthermore, the medical device can comprise a tubular member having asidewall and a plurality of pores in the sidewall that are sized toinhibit flow of blood through the sidewall into an aneurysm to a degreesufficient to lead to thrombosis and healing of the aneurysm when thetubular member is positioned in a blood vessel and adjacent to theaneurysm. The device can also have an anti-thrombogenic coatingdistributed over the tubular member such that the pores aresubstantially free of webs formed by the coating.

The pores can have an average pore size that is the average size of thepores in the first section without the coating material. The coating canbe substantially complete over the device or tubular member. The coatingcan be generally uniform over the device or tubular member. The deviceor tubular member can comprise a plurality of braided filaments. Thedevice or tubular member can be substantially free of webs formedbetween the braided filaments by the coating. The flow diverting porescan extend over less than a longitudinal length that is less than alongitudinal length of the device or tubular member.

The device can comprise a tubular member comprising a plurality offilaments that are braided together to form pores therebetween. Thetubular member can have a flow diverting section configured to span theneck of the aneurysm. The device can also have a coating distributedover the flow diverting section. The coating is distributed completelyover the flow diverting section substantially free of imperfections suchthat coated first and second longitudinal segments of the flow divertingsection of approximately the same longitudinal lengths haveapproximately equal weights.

A medical device for treating an aneurysm can also be provided thatcomprises a tubular member comprising a plurality of filaments, formedfrom a first material, that are braided together to form porestherebetween. The device can also comprise a coating materialdistributed over the filaments to form a coated flow diverting sectionthat is substantially free of webs formed between the filaments by thecoating material. The coating material can be distributed such that thedevice is significantly less thrombogenic than an uncoated device formedfrom the first material.

The coating material can be one or more of a variety ofanti-thrombogenic materials or platelet aggregation inhibitors, oranti-thrombogenic polymers or monomers. Suitable coating materialsinclude 2-Methacryloyloxyethyl phosphorylcholine (MPC, available asLIPIDURE™ from NOF Corporation of Tokyo, Japan). A suitable form of MPCis LIPIDURE™-CM2056, or 2-Methacryloyloxyethylphosphorylcholine-poly(n-butyl methacrylate). Additional suitablecoating materials include PARYLENE C™, or PARYLENE HT™, both availablefrom Specialty Coating Systems of Indianapolis, Ind.; BAYMEDIX™available from Bayer AG of Leverkusen, Germany; BIOCOAT™ hyaluronic acidavailable from BioCoat, Inc. of Horsham, Pa.; or polyethylene oxide.Other coating materials include heparin, heparin-like materials orderivatives, hirudin, H-Heparin, HSI-Heparin, albumin, phospholipids,streptokinase, tissue plasminogen activator (TPA), urokinase, hyaluronicacid, chitosan, methyl cellulose, poly(ethylene oxide), poly(vinylpyrrolidone), endothelial cell growth factor, epithelial growth factor,osteoblast growth factor, fibroblast growth factor, platelet derivedgrowth factor or angiogenic growth factor.

In some embodiments, the pores can have an average pore size that isless than or equal to about 500 microns. The pores can have an averagepore size that is less than or equal to about 320 microns. The pores canhave an average pore size that is from about 50 microns to about 320microns. The pores can have a pore size that is generally constant. Thepores can have an average pore size that is measured using an inscribedcircle diameter.

Some embodiments of processes disclosed herein comprise mounting ormaintaining a braided, flow diverting device (e.g., stent) in alongitudinally stretched configuration during the coating process inorder to prevent coating imperfections, such as webbing. Thelongitudinally stretched configuration can enable individual filamentsof the braided device to overlap each other at angles of between about75 degrees and about 105 degrees with respect to each other. Thelongitudinally stretched configuration can enable individual filamentsof the braided device to overlap each other at angles of between about80 degrees and about 100 degrees with respect to each other. Further,the longitudinally stretched configuration can enable individualfilaments of the braided device to overlap each other at angles ofbetween about 85 degrees and about 95 degrees with respect to eachother. Furthermore, the longitudinally stretched configuration canenable individual filaments of the braided device to overlap each otherapproximately perpendicularly or at a generally right angles withrespect to each other. In some embodiments, therefore, thelongitudinally stretched configuration can orient the individualfilaments to create a pattern of quadrilaterals, such as squares,rectangles, parallelograms, rhombuses, trapezoids, etc.

Further, some embodiments of processes disclosed herein comprise dippinga longitudinally stretched braided device (e.g., stent) in a coatingsolution and thereafter air knifing the dipped device. The process ofair knifing can comprise applying at least one powerful jet of air toremove or blow off any excess solution from the device. The air jet(s)of the air knife(s) can be applied in a direction that is generallytransverse, such as orthogonal, relative to the longitudinal axis of thedevice. The air knife can be stationary while the device is moved or itcan move along and/or about the device as the device remains stationary.

In some embodiments, the longitudinally stretched braided device (e.g.,stent) can alternatively be coated with a coating solution using aspraying operation. In some embodiments, while the device is beingcoated, the device can be rotated about its central longitudinal axis toensure even application of the air jet or sprayed coating.

For example, a method of coating a stent is provided wherein the methodcomprises: attaching first and second ends of the stent with upper andlower connectors of a holder device, the stent comprising a flowdiverting section; dipping the stent into a coating material to coat afirst section of the stent; and removing excess coating material fromthe stent such that the stent is free of webs formed by the coatingmaterial.

The method can be performed such that the flow diverting sectioncomprises a plurality of pores having an average pore size that is lessthan or equal to about 500 microns. Further, the average pore size canbe less than or equal to about 320 microns. The average pore size can befrom about 50 microns to about 320 microns.

The method can be performed such that dipping the stent into the coatingmaterial comprises dipping less than an entire length of the stent intothe coating material to maintain an open air pocket adjacent to thestent first end. Further, attaching the first and second ends of thestent can comprise attaching the stent to the holder device such thatthe stent is held between the upper and lower connectors in a radiallycollapsed, longitudinally elongated state. The stent can comprise aplurality of braided filaments, and the stent filaments can cross eachother at substantially right angles when the stent is held in theelongated state. Further, the elongated state can be achieved when thestent filaments cross each other at angles in an angular range fromabout 80° to about 110°. In addition, the stent can comprise a pluralityof braided filaments, and the coating material on the stent can besubstantially free of webs such that the coating material does notbridge between adjacent filaments.

Additionally, some embodiments of the coating (e.g., dipping, spraying,etc.) processes disclosed herein can be performed using a cantileveredfixture. One of the inventive realizations of some embodiments is that acantilevered fixture, which can be suitable for use in, for example, adipping process, can also be designed to be suitable for use in airknifing processes, when necessary. In order to be suitable for airknifing processes, however, the cantilevered fixture can beneficially beconfigured to resist deflection, such as the “pendulum effect” thatoccurs when an air jet is applied to the mounted device, and the deviceand the fixture begin to move back and forth harmonically, off-axis.Further, the cantilevered fixture can also beneficially be configured tomount the device thereto without passing through a lumen of the deviceor otherwise interfering with air flow from the air knife. Furthermore,the cantilevered fixture can also beneficially avoid contact with thedevice in order to prevent wicking or removing solution from the surfaceof the device.

Accordingly, in some embodiments, the cantilevered fixture can be bothrigid and lightweight. For example, a lower (free) end of thecantilevered fixture can be lighter weight than an upper (cantilevered)end of the cantilevered fixture.

Further, in some embodiments, the cantilevered fixture can comprisefirst and second ends that engage with corresponding ends of the device(e.g., stent) and a fixture body that extends between the first andsecond ends and outside of a device lumen when the device is mounted tothe fixture. The first end can comprise one or more clips or protrusionsthat engage a first end of the device, such as by pinching, grasping,friction, and/or hook and loop, or other mechanical fastening means. Thesecond end can comprise one or more clips or protrusions that engage anopposing end of the device, such as by pinching, grasping, friction,and/or a hook and loop or other mechanical fastening means. The firstand second ends can be upper or lower ends of the cantilevered fixture.The first and second ends can be spaced apart sufficiently to maintainthe device in a longitudinally stretched configuration when mounted onthe cantilevered fixture.

In accordance with some embodiments, a method of coating a stent isprovided in which the method comprises: attaching a first end of thestent with an upper connector of a holder device, the stent comprising aplurality of braided filaments; attaching a second end of the stent witha lower connector of the holder device such that the stent is heldbetween the upper and lower connectors in a radially collapsed,longitudinally elongated state, the stent filaments crossing each otherat substantially right angles when the stent is held in the elongatedstate; while maintaining the stent in the elongated state, dipping thestent into a coating material to coat a first section of the stent; andremoving excess coating material from the stent.

The elongated state can be achieved when the stent filaments cross eachother at angles ranging from about 80° to about 110°. Further, theelongated state can be achieved when the stent filaments cross eachother at angles in a range from about 85° to about 95°.

The method can be performed such that removing excess coating materialcomprises applying a stream of gas to the stent filaments. The stream ofgas can be of a sufficient strength to remove excess coating materialfrom the stent. Further, removing excess coating material can compriserotating the stent and holder device while applying a stream of gas toimpinge upon an outer surface of the stent. Furthermore, the method cancomprise drying the coating material applied to the stent. For example,the drying can comprise drying the stent in an oven at between fromabout 50° to about 80° for between from about 5 minutes to about 1 hour,and in some embodiments, at about 60° for about 15 minutes.

The method can be performed such that dipping the stent into the coatingmaterial comprises dipping less than an entire length of the stent intothe coating material to maintain an open air pocket adjacent to thestent first end. Further, the holder device upper and lower connectorscan be interconnected such that the holder device is in a cantileveredconfiguration during the dipping and removing steps.

In some embodiments, a method of coating a stent can be provided thatcomprises: attaching a first end of the stent with an upper connector ofa holder device, the stent comprising a plurality of braided filamentsand a plurality of pores located between the filaments; attaching asecond end of the stent with a lower connector of the holder device suchthat the stent is held between the upper and lower connectors in aradially collapsed, longitudinally elongated state in which thefilaments are oriented to substantially maximize an average inscribedarea of the pores; while maintaining the stent in the elongated state,dipping the stent into a coating material to coat a first section of thestent; and removing excess coating material from the stent.

The method can be performed such that the maximum average inscribed areaof the pores is achieved when the filaments cross each other atsubstantially right angles. The maximum average inscribed area of thepores can be achieved when the pores are substantially square. Themaximum average inscribed area of the pores can be achieved when thefilaments cross each other at angles in a range from about 80° to about110°. Further, the maximum average inscribed area of the pores can beachieved when the filaments cross each other at angles in a range fromabout 85° to about 95°.

The subject technology is illustrated, for example, according to variousaspects described below. Various examples of aspects of the subjecttechnology are described as numbered clauses (1, 2, 3, etc.) forconvenience. These are provided as examples and do not limit the subjecttechnology. It is noted that any of the dependent clauses may becombined in any combination, and placed into a respective independentclause, e.g., clause 1 or clause 5. The other clauses can be presentedin a similar manner.

Clause 1. A medical device for treating an aneurysm, comprising:

-   -   a tubular body configured to be implanted in a blood vessel and        comprising a plurality of braided filaments, the body being        expandable to an expanded state for treatment of the aneurysm,        the body having a first section for spanning the neck of the        aneurysm and a plurality of pores located between the filaments,        the pores in the first section having a first average pore size        of less than about 500 microns when the body is in the expanded        state;    -   the first section having a substantially complete coating,        comprising a coating material, over the filaments;    -   wherein the first section is substantially free of webs formed        between the braided filaments by the coating material.

Clause 2. The medical device of Clause 1, wherein the first average poresize is less than or equal to about 320 microns.

Clause 3. The medical device of Clause 2, wherein the first average poresize is from about 50 microns to about 320 microns.

Clause 4. The medical device of Clause 1, wherein the first average poresize is measured using an inscribed circle diameter.

Clause 5. The medical device of Clause 1, wherein the first average poresize is the average size of the pores in the first section without thecoating material.

Clause 6. The medical device as in Clause 1, wherein the first sectioncomprises less than an entire length of the tube.

Clause 7. The medical device as in Clause 1, wherein the coatingmaterial on the first section is generally uniform over the filaments.

Clause 8. The medical device as in Clause 1, wherein the coatingcomprises an antithrombogenic material.

Clause 9. The medical device as in Clause 8, wherein the coatingcomprises an antithrombogenic polymer.

Clause 10. The medical device as in Clause 8, wherein the coatingcomprises MPC.

Clause 11. The medical device as in Clause 1, further comprising asecond section having a plurality of pores having a second average poresize greater than the first average pore size.

Clause 12. The medical device as in Clause 1, wherein the first sectioncomprises a circumferential portion of the device that is at least 5 mmin length.

Clause 13. A delivery system for treating an aneurysm, the systemcomprising:

-   -   a microcatheter configured to be implanted into a blood vessel;    -   a core assembly, extending within the microcatheter, having a        distal segment; and    -   the device of Clause 1 extending along the core assembly distal        segment.

Clause 14. The medical device as in Clause 1, wherein the filamentscomprise heat-treated metallic filaments.

Clause 15. The medical device as in Clause 1, wherein the tubular bodycomprises a heat-set metallic braid.

Clause 16. The medical device as in Clause 1, wherein the tubular bodyis self-expanding.

Clause 17. The medical device as in Clause 1, wherein the device is lessthrombogenic than an identical, uncoated device.

Clause 18. The medical device as in Clause 17, wherein the deviceexhibits an elapsed time before peak thrombin formation that is at least1.5 times the elapsed time of the identical, uncoated device.

Clause 19. The medical device as in Clause 1, wherein the tubular bodyhas an open proximal end, an open distal end, and forms a lumenextending from the proximal end to the distal end.

Clause 20. A medical device for treating an aneurysm, comprising:

-   -   a tubular member having a sidewall and a plurality of pores in        the sidewall that are sized to inhibit flow of blood through the        sidewall into an aneurysm to a degree sufficient to lead to        thrombosis and healing of the aneurysm when the tubular member        is positioned in a blood vessel and adjacent to the aneurysm;        and    -   an anti-thrombogenic coating distributed over the tubular member        such that the pores are substantially free of webs formed by the        coating.

Clause 21. The medical device of Clause 20, wherein the pores have anaverage pore size that is less than or equal to about 500 microns.

Clause 22. The medical device of Clause 21, wherein the pores have anaverage pore size that is less than or equal to about 320 microns.

Clause 23. The medical device of Clause 22, wherein the pores have anaverage pore size that is from about 50 microns to about 320 microns.

Clause 24. The medical device of Clause 20, wherein the pores have anaverage pore size that is measured using an inscribed circle diameter.

Clause 25. The medical device of Clause 20, wherein the pores have anaverage pore size that is the average size of the pores in the firstsection without the coating material.

Clause 26. The device of Clause 20, wherein the coating is substantiallycomplete over the tubular member.

Clause 27. The device of Clause 26, wherein the coating is generallyuniform over the tubular member.

Clause 28. The device of Clause 20, wherein the coating is substantiallycomplete over at least a circumferential section of the device that is 5mm or more in length.

Clause 29. The medical device of Clause 20, wherein the tubular membercomprises a plurality of braided filaments.

Clause 30. The medical device as in Clause 29, wherein the filamentscomprise heat-treated metallic filaments.

Clause 31. The medical device as in Clause 29, wherein the tubularmember comprises a heat-set metallic braid.

Clause 32. The medical device as in Clause 29, wherein the tubularmember is substantially free of webs formed between the braidedfilaments by the coating.

Clause 33. The medical device as in Clause 20, wherein the tubularmember is self-expanding.

Clause 34. The medical device of Clause 20, wherein the flow divertingpores extend over less than a longitudinal length that is less than alongitudinal length of the tubular member.

Clause 35. The medical device as in Clause 20, wherein the device isless thrombogenic than an identical, uncoated device.

Clause 36. The medical device as in Clause 35, wherein the deviceexhibits an elapsed time before peak thrombin formation that is at least1.5 times the elapsed time of the identical, uncoated device.

Clause 37. The medical device as in Clause 20, wherein the tubular bodyhas an open proximal end, an open distal end, and forms a lumenextending from the proximal end to the distal end.

Clause 38. A medical device for treating an aneurysm, comprising:

-   -   a tubular member comprising a plurality of filaments that are        braided together to form pores therebetween, the tubular member        having a flow diverting section configured to span the neck of        the aneurysm; and    -   a coating distributed over the flow diverting section;    -   wherein the coating is distributed completely over the flow        diverting section substantially free of imperfections such that        coated first and second longitudinal segments of the flow        diverting section of approximately the same longitudinal lengths        have approximately equal weights.

Clause 39. The medical device of Clause 38, wherein the pores in theflow diverting section have an average pore size that is less than orequal to about 500 microns.

Clause 40. The medical device of Clause 39, wherein the average poresize is less than or equal to about 320 microns.

Clause 41. The medical device of Clause 40, wherein the average poresize is from about 50 microns to about 320 microns.

Clause 42. The medical device of Clause 38, wherein the pores in theflow diverting section have a pore size that is generally constant.

Clause 43. The medical device of Clause 38, wherein the coating isgenerally uniform over the flow diverting section.

Clause 44. The medical device as in Clause 38, wherein the filamentscomprise heat-treated metallic filaments.

Clause 45. The medical device as in Clause 38, wherein the tubularmember comprises a heat-set metallic braid.

Clause 46. A method of coating a stent, the method comprising:

-   -   attaching first and second ends of the stent with upper and        lower connectors of a holder device, the stent comprising a flow        diverting section;    -   dipping the stent into a coating material to coat a first        section of the stent; and    -   removing excess coating material from the stent such that the        stent is free of webs formed by the coating material.

Clause 47. The method of Clause 46, wherein the flow diverting sectioncomprises a plurality of pores having an average pore size that is lessthan or equal to about 500 microns.

Clause 48. The method of Clause 47, wherein the average pore size isless than or equal to about 320 microns.

Clause 49. The method of Clause 48, wherein the average pore size isfrom about 50 microns to about 320 microns.

Clause 50. The method of Clause 46, wherein dipping the stent into thecoating material comprises dipping less than an entire length of thestent into the coating material to maintain an open air pocket adjacentto the stent first end.

Clause 51. The method of Clause 46, wherein attaching the first andsecond ends of the stent comprises attaching the stent to the holderdevice such that the stent is held between the upper and lowerconnectors in a radially collapsed, longitudinally elongated state.

Clause 52. The method of Clause 51, wherein the stent comprises aplurality of braided filaments, and wherein the stent filaments crosseach other at substantially right angles when the stent is held in theelongated state.

Clause 53. The method of Clause 52, wherein the elongated state isachieved when the stent filaments cross each other at angles in anangular range from about 80° to about 110°.

Clause 54. The method of Clause 46, wherein the stent comprises aplurality of braided filaments, and the coating material on the stent issubstantially free of webs such that the coating material does notbridge between adjacent filaments.

Clause 55. A method of coating a stent, the method comprising:

-   -   attaching a first end of the stent with an upper connector of a        holder device, the stent comprising a plurality of braided        filaments;    -   attaching a second end of the stent with a lower connector of        the holder device such that the stent is held between the upper        and lower connectors in a radially collapsed, longitudinally        elongated state, the stent filaments crossing each other at        substantially right angles when the stent is held in the        elongated state;    -   while maintaining the stent in the elongated state, dipping the        stent into a coating material to coat a first section of the        stent; and    -   removing excess coating material from the stent.

Clause 56. The method of Clause 55, wherein the elongated state isachieved when the stent filaments cross each other at angles in anangular range from about 80° to about 110°.

Clause 57. The method of Clause 56, wherein the elongated state isachieved when the stent filaments cross each other at angles in anangular range from about 85° to about 95°.

Clause 58. The method of Clause 55, wherein removing excess coatingmaterial comprises applying a stream of gas to the stent filaments, thestream of gas being of a sufficient strength to remove excess coatingmaterial from the stent.

Clause 59. The method of Clause 55, wherein removing excess coatingmaterial comprises rotating the stent and holder device while applying astream of gas to impinge upon an outer surface of the stent.

Clause 60. The method of Clause 55, further comprising drying thecoating material applied to the stent.

Clause 61. The method of Clause 55, wherein dipping the stent into thecoating material comprises dipping less than an entire length of thestent into the coating material to maintain an open air pocket adjacentto the stent first end.

Clause 62. The method of Clause 55, wherein the holder device upper andlower connectors are interconnected such that the holder device is in acantilevered configuration during the dipping and removing steps.

Clause 63. A method of coating a stent, the method comprising:

-   -   attaching a first end of the stent with an upper connector of a        holder device, the stent comprising a plurality of braided        filaments and a plurality of pores located between the        filaments;    -   attaching a second end of the stent with a lower connector of        the holder device such that the stent is held between the upper        and lower connectors in a radially collapsed, longitudinally        elongated state in which the filaments are oriented to        substantially maximize an average inscribed area of the pores;    -   while maintaining the stent in the elongated state, dipping the        stent into a coating material to coat a first section of the        stent; and    -   removing excess coating material from the stent.

Clause 64. The method of Clause 63, wherein the maximum averageinscribed area of the pores is achieved when the filaments cross eachother at substantially right angles.

Clause 65. The method of Clause 63, wherein the maximum averageinscribed area of the pores is achieved when the pores are substantiallysquare.

Clause 66. The method of Clause 63, wherein the maximum averageinscribed area of the pores is achieved when the filaments cross eachother at angles in an angular range from about 80° to about 110°.

Clause 67. The method of Clause 66, wherein the maximum averageinscribed area of the pores is achieved when the filaments cross eachother at angles in an angular range from about 85° to about 95°.

Clause 68. A medical device for treating an aneurysm, the devicecomprising:

-   -   a tubular member comprising a plurality of filaments, formed        from a first material, that are braided together to form pores        therebetween; and    -   a coating material distributed over the filaments to form a        coated flow diverting section that is substantially free of webs        formed between the filaments by the coating material, the        coating material distributed such that the device is less        thrombogenic than a similar but uncoated device.

Clause 69. The device of Clause 68, wherein the coating materialcomprises an antithrombogenic polymer.

Clause 70. The device of Clause 68, wherein the coating materialcomprises MPC.

Clause 71. The device of Clause 68, wherein the coating materialcomprises MPC.

Clause 72. The device of Clause 68, wherein the filaments compriseheat-treated metallic filaments.

Clause 73. The medical device as in Clause 68, wherein the tubularmember is self-expanding.

Clause 74. The medical device as in Clause 68, wherein the deviceexhibits an elapsed time before peak thrombin formation that is at least1.5 times the elapsed time of the similar, uncoated device.

Clause 75. A method of treating an aneurysm formed in a wall of a parentblood vessel, the method comprising:

-   -   deploying the medical device of any preceding Clause into the        parent blood vessel so that a sidewall of the medical device        extends across a neck of the aneurysm, thereby causing        thrombosis within the aneurysm.

Clause 76. A method of treating an aneurysm formed in a wall of a parentblood vessel of a patient, the method comprising:

-   -   deploying a coated, low-thrombogenicity flow-diverting stent in        the parent blood vessel across the neck of the aneurysm, so as        to treat the aneurysm; and    -   either (a) prescribing to the patient a reduced protocol of        blood-thinning medication, in comparison to a protocol that        would be prescribed to the patient if an otherwise similar but        uncoated, non-low-thrombogenicity stent were deployed in the        patient, or (b) declining to prescribe to the patient any        blood-thinning medication.

Clause 77. The method of Clause 76, wherein the stent comprises themedical device of any preceding Clause.

Clause 78. The method of Clause 76, wherein the patient is one who hasbeen diagnosed as being at risk of an intracranial hemorrhage.

Clause 79. The method of Clause 76, wherein the patient is one who hasbeen diagnosed as being at risk of a cerebral hemorrhage from ananeurysm.

Clause 80. The method of Clause 76, wherein the parent blood vessel isan intracranial artery.

Clause 81. The method of Clause 76, further comprising accessing atreatment region near the aneurysm by inserting a microcatheter into theparent vessel, and delivering the stent through the microcatheter to thetreatment region.

Clause 82. The method of Clause 76, wherein the stent exhibits anelapsed time before peak thrombin formation that is at least 1.5 timesthe elapsed time of the similar but uncoated stent.

Clause 83. A method of treating an aneurysm formed in a wall of a parentblood vessel of a patient, the method comprising:

-   -   deploying a flow-diverting stent in the parent blood vessel        across the neck of the aneurysm, so as to treat the aneurysm, at        least a portion of the stent being coated with an        anti-thrombogenic material so that the stent exhibits an elapsed        time before peak thrombin formation that is at least 1.5 times        the elapsed time of an otherwise similar but uncoated stent; and    -   either (a) prescribing to the patient a reduced protocol of        blood-thinning medication, in comparison to a protocol that        would be prescribed to the patient if the otherwise similar but        uncoated stent were deployed in the patient, or (b) declining to        prescribe to the patient any blood-thinning medication.

Clause 84. The method of Clause 83, wherein the stent comprises themedical device of any preceding Clause.

Clause 85. The method of Clause 83, wherein the patient is one who hasbeen diagnosed as being at risk of an intracranial hemorrhage.

Clause 86. The method of Clause 83, wherein the patient is one who hasbeen diagnosed as being at risk of a cerebral hemorrhage from ananeurysm.

Clause 87. The method of Clause 83, wherein the parent blood vessel isan intracranial artery.

Clause 88. The method of Clause 83, further comprising accessing atreatment region near the aneurysm by inserting a microcatheter into theparent vessel, and delivering the stent through the microcatheter to thetreatment region.

Clause 89. A medical device for treating an aneurysm, comprising:

-   -   a tubular member comprising a plurality of braided filaments        that form a sidewall and a plurality of pores in the sidewall        that are sized to inhibit flow of blood through the sidewall        into an aneurysm to a degree sufficient to lead to thrombosis        and healing of the aneurysm when the tubular member is        positioned in a blood vessel and adjacent to the aneurysm; and    -   an anti-thrombogenic material distributed over the tubular        member such that the pores are substantially free of webs formed        by the material;    -   wherein the tubular member exhibits an elapsed time before peak        thrombin formation that is at least 1.5 times the elapsed time        of an identical, uncoated tubular member.

Clause 90. The medical device of Clause 89, wherein the pores have anaverage pore size that is less than or equal to about 500 microns.

Clause 91. The medical device of Clause 89, wherein the pores have anaverage pore size that is less than or equal to about 320 microns.

Clause 92. The medical device of Clause 91, wherein the pores have anaverage pore size that is measured using an inscribed circle diameter.

Clause 93. The medical device of Clause 89, wherein the distribution ofthe anti-thrombogenic material is substantially complete over thetubular member.

Clause 94. The medical device of Clause 93, wherein theanti-thrombogenic material is generally uniform over the tubular member.

Clause 95. The medical device of Clause 89, wherein the distribution ofthe anti-thrombogenic material is substantially complete over at least acircumferential section of the tubular member that is 5 mm or more inlength.

Clause 96. The medical device of Clause 95, wherein theanti-thrombogenic material comprises an anti-thrombogenic polymer.

Clause 97. The medical device of Clause 96, wherein theanti-thrombogenic polymer comprises MPC.

Clause 98. The medical device of Clause 89, wherein the tubular membercomprises a heat-set metallic braid.

Clause 99. The medical device of Clause 89, wherein the tubular memberis self-expanding.

Clause 100. The medical device of Clause 89, wherein the tubular memberhas an open proximal end, an open distal end, and forms a lumenextending from the proximal end to the distal end.

Clause 101. The medical device of Clause 89, wherein the tubular memberexhibits an elapsed time before peak thrombin formation that is at least2.5 times the elapsed time of an identical, uncoated tubular member.

Clause 102. The medical device of Clause 89, wherein the tubular memberhas an expanded diameter, and an unexpanded diameter smaller than theexpanded diameter, and the unexpanded diameter is 5 mm or less.

Clause 103. The medical device of Clause 102, wherein the unexpandeddiameter is 3 mm or less.

Clause 104. A delivery system for treating an aneurysm, the systemcomprising:

-   -   an elongate core assembly comprising a tube, a wire, or a        combination of a tube and a wire; and    -   the medical device of Clause 89 engaged with the core assembly        so as to be movable via the core assembly.

Clause 105. The delivery system of Clause 104, further comprising amicrocatheter configured to be implanted into a blood vessel, whereinthe core assembly is configured to extend within the microcatheter.

Clause 106. The delivery system of Clause 104, further comprising apolymeric member that engages an inner wall of the tubular body andenables longitudinal force transmission from the core assembly to thetubular body.

Clause 107. A medical device for treating an aneurysm, comprising:

-   -   a tubular body configured to be implanted in a blood vessel and        comprising a plurality of braided filaments, the body being        expandable to an expanded state for treatment of the aneurysm,        the body having a first section for spanning the neck of the        aneurysm and a plurality of pores located between the filaments,        the pores in the first section having a first average pore size        of less than about 500 microns when the body is in the expanded        state;    -   the first section having a substantially complete distribution        of anti-thrombogenic material over the filaments;    -   wherein the first section is substantially free of webs formed        between the braided filaments by the anti-thrombogenic material;    -   wherein the tubular body exhibits an elapsed time before peak        thrombin formation that is at least 1.5 times the elapsed time        of an identical, uncoated tubular body.

Clause 108. The medical device of Clause 107, wherein the first averagepore size is less than or equal to about 320 microns.

Clause 109. The medical device of Clause 107, wherein the first averagepore size is measured using an inscribed circle diameter.

Clause 110. The medical device of Clause 107, wherein the first averagepore size is the average size of the pores in the first section withoutthe anti-thrombogenic material.

Clause 111. The medical device of Clause 107, wherein the first sectioncomprises less than an entire length of the tube.

Clause 112. The medical device of Clause 107, wherein theanti-thrombogenic material on the first section is generally uniformover the filaments.

Clause 113. The medical device of Clause 107, wherein theanti-thrombogenic material comprises an anti-thrombogenic polymer.

Clause 114. The medical device of Clause 113, wherein theanti-thrombogenic polymer comprises MPC.

Clause 115. The medical device of Clause 107, wherein the tubular bodycomprises a heat-set metallic braid.

Clause 116. The medical device of Clause 107, wherein the tubular bodyis self-expanding.

Clause 117. The medical device of Clause 107, wherein the tubular bodyhas an open proximal end, an open distal end, and forms a lumenextending from the proximal end to the distal end.

Clause 118. The medical device of Clause 107, wherein the tubular bodyexhibits an elapsed time before peak thrombin formation that is at least2.5 times the elapsed time of an identical, uncoated tubular member.

Clause 119. The medical device of Clause 107, wherein the tubular bodyhas an expanded diameter, and an unexpanded diameter smaller than theexpanded diameter, and the unexpanded diameter is 5 mm or less.

Clause 120. The medical device of Clause 119, wherein the unexpandeddiameter is 3 mm or less.

Clause 121. A delivery system for treating an aneurysm, the systemcomprising:

-   -   an elongate core assembly comprising a tube, a wire, or a        combination of a tube and a wire; and    -   the medical device of Clause 107 engaged with the core assembly        so as to be movable via the core assembly.

Clause 122. The delivery system of Clause 121, further comprising amicrocatheter configured to be implanted into a blood vessel, whereinthe core assembly is configured to extend within the microcatheter.

Clause 123. The delivery system of Clause 121, further comprising apolymeric member that engages an inner wall of the tubular body andenables longitudinal force transmission from the core assembly to thetubular body.

Additional features and advantages of the subject technology will be setforth in the description below, and in part will be apparent from thedescription, or may be learned by practice of the subject technology.The advantages of the subject technology will be realized and attainedby the structure particularly pointed out in the written description andembodiments hereof as well as the appended drawings.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory and areintended to provide further explanation of the subject technology.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are included to provide furtherunderstanding of the subject technology and are incorporated in andconstitute a part of this specification, illustrate aspects of thedisclosure and together with the description serve to explain theprinciples of the subject technology.

FIG. 1 is a perspective view of a device, illustrated as a stent, havinga coating applied using a prior art method, illustrating webbing of thecoating.

FIG. 2 is an enlarged view of a stent having a coating applied using aprior art method, illustrating delamination of the coating.

FIGS. 3A-3C are enlarged views of a stent having a coating applied usinga prior art method, illustrating accumulation of excess coating materialand webbing.

FIG. 4 is a side view of a stent comprising a coating, according to someembodiments.

FIG. 5A is an enlarged view of the stent shown in FIG. 4, according tosome embodiments.

FIGS. 5B-5C are detail views of a pore of the stent of FIG. 4, invarious conditions.

FIG. 6 is a side view of a coating system having a stent mounted thereonin a first position in preparation for coating the stent, according tosome embodiments.

FIG. 7A is a side view of the coating system of FIG. 6, wherein thestent has been immersed in a coating solution, according to someembodiments.

FIG. 7B is a detail view of the dipping procedure near an upper end ofthe stent being dipped.

FIG. 8A is a side view of the coating apparatus of FIG. 6, wherein thestent is removed from the coating solution and coating solution isremoved, according to some embodiments.

FIG. 8B is a detail view of an air knifing procedure being carried outon the stent with the coating system of FIG. 6.

FIG. 9A is a side view of the coating apparatus of FIG. 6, wherein thestent has been returned to the first position.

FIG. 9B is a detailed side view of a stent mounting apparatus for usewith the coating system of FIG. 6.

FIG. 9C is a detailed front view of the stent mounting apparatus of FIG.9B.

FIG. 9D is a detailed view of a lower fixture of the stent mountingapparatus of FIGS. 9B-9C.

FIG. 10 is a side view of the mounting apparatus of FIGS. 9B-9D, with astent mounted thereon.

FIG. 11 is an enlarged view of an upper bracket of the mountingapparatus of FIGS. 9B-10, according to some embodiments.

FIG. 12 is an enlarged view of a lower bracket of the mounting apparatusof FIGS. 9B-11, according to some embodiments.

FIG. 13 is an enlarged view of a stent mounted on the mounting apparatusof FIGS. 9B-12 in a stretched configuration, according to someembodiments.

FIG. 14A is an enlarged view of a coated stent in a relaxedconfiguration, demonstrating no visible webbing or delamination,according to some embodiments.

FIG. 14B is a detailed view of a filament crossing point of a coatedstent.

FIG. 15 is a chart of weight gain measured in series of longitudinalsections of six coated stents.

FIGS. 16A-16C are views of a stent coated according to some embodiments,demonstrating no webbing or delamination of the coating.

FIGS. 17A-17C are views of another stent coated according to someembodiments, demonstrating no webbing or delamination of the coating.

FIGS. 18A-18C are views of yet another stent coated according to someembodiments, demonstrating no webbing or delamination of the coating.

FIGS. 19A-19C are views of yet another stent coated according to someembodiments, demonstrating no webbing or delamination of the coating.

FIG. 20 is a views of yet another stent coated according to someembodiments, demonstrating no webbing or delamination of the coating.

DETAILED DESCRIPTION

In the following detailed description, numerous specific details are setforth to provide a full understanding of the subject technology. Itshould be understood that the subject technology may be practicedwithout some of these specific details. In other instances, well-knownstructures and techniques have not been shown in detail so as not toobscure the subject technology. Further, although the present disclosuremay refer to embodiments in which the apparatus is a stent, aspects ofthe embodiments disclosed herein can be used with any implantabledevice, such as coils, filters, scaffolds, self-expanding andballoon-expandable stents, and other devices.

In accordance with some embodiments disclosed herein, a heat-treateddevice (e.g., stent) is provided that comprises an even coating that issubstantially free of imperfections, such as lumps, fibers, webs, and/orother obstructions in the pores of the device. Further, in someembodiments, such a device can be braided and/or have a flow divertingsection.

To the Applicants' knowledge, the devices and methods disclosed hereinhave not been available or possible based on prior devices and methodsof manufacture. In general, prior coated devices, such as stents, havedemonstrated various coating imperfections and resultant disadvantages.

Among these disadvantages, “webbing,” delamination, and uneven layeringof coating material pose significant risks. “Webbing” of coatingmaterial occurs when the coating material spans or extends betweenfilaments of a device to create a thin, localized film of coatingmaterial between the filaments. Delamination occurs when coatingmaterial peels away from or is not bound to the device filaments. Unevenlayering of coating material can exacerbate the effects of delaminationand webbing, creating large pieces of coating that do not easilydissolve or pass through a blood vessel when such pieces are dislodged.Webbing and delamination create a significant risk to proper blood flowif that coating material is dislodged or breaks free from the devicefilaments. If this occurs, the dislodged coating material can create orcontribute to blockages in the blood vessel. This is a dangerouscondition that can result from certain prior art devices and coatingprocesses.

For example, referring to FIG. 1, a braided stent 10 illustratesproblems that can arise when the stent 10 is coated with a coatingmaterial. As shown, the coating material (which appears in FIG. 1 as therelatively brighter portions of the stent 10) is distributed generallyunevenly along the braided stent 10 and has spanned between adjacentfilaments to produce “webs” or “webbing” between the filaments of thebraided stent 10.

FIG. 2 is a high magnification view of a braided stent 20 coated with acoating material 22 that has delaminated. The delaminated coatingmaterial 22 can easily break free from the stent, as discussed below.FIGS. 3A-C also illustrate other views of a stent 30 having excesscoating and delamination.

Typically, a braided vascular device such as a stent is braided fromfilaments which are formed from metal alloys and/or otherhigh-temperature materials. The resulting braid is then heat-treated or“heat-set” at high temperature in order to reduce internal stresses inthe filaments and increase the self-expanding capability of the stent.The prevalence of heat treatment and need for self-expanding propertiesin the manufacture of braided vascular devices and stents negates thepossibility of “pre-coating” the individual filaments with alow-temperature material such as a polymer, a drug or a drug carrier andthen braiding the pre-coated filaments to form a device which must thenbe heat-treated. Truly, a person of skill has had no expectation ofsuccessfully braiding filaments that have been pre-coated with any ofthe low-temperature materials that make up the bulk of useful coatings,and later heat setting the braided device to create a coated, heat-setdevice because of the significant damage the heat would cause to thecoating.

Furthermore, no prior device or method of manufacturing known to theApplicants has been able to produce a heat-treated, coated, braidedimplantable device with a small pore size that is free of thedisadvantages of webbing, delamination, and uneven layering of coatingmaterial, which is now possible in accordance with some implementationsof the present disclosure. Again, given the exceedingly small pore size,a person of skill has had no expectation of successfully coating such adevice evenly and without the disadvantages of webbing, delamination, orother coating imperfections. FIGS. 1-3C demonstrate the difficulty ofcoating such small-pore-size devices.

Indeed, to the present knowledge of the Applicants, no prior devices ormethods of manufacture have been developed that produce a coated device(e.g., stent) having a flow diverting section that is substantially freeof the disadvantages noted above. As discussed herein, a flow divertingsection can have pores with a “flow diverting pore size.” A “flowdiverting pore size” can refer to an average pore size of pores (in atleast a section of a device) that is sufficiently small enough tointerfere with or inhibit fluid exchange through the pores of thatsection. For example, a device (e.g., stent) can have an active sectionor a flow diverting section with a flow diverting pore size when thepores of the section are sized to inhibit flow of blood through thesidewall into an aneurysm to a degree sufficient to lead to thrombosisand healing of the aneurysm when the tubular member is positioned in ablood vessel and adjacent to or across the neck of the aneurysm.

For example, a flow diverting pore size can be achieved when pores inthe flow diverting or active section (or in the stent as a whole) havean average pore size of less than about 500 microns when the device(e.g., stent) is in the expanded state. (When “expanded state” is usedherein to specify braided stent parameters such as pore sizes, theexpanded state is one that the stent will self-expand to without anyexternal expansive forces applied, and without any external longitudinalstretching or compressive forces applied. For simplicity of measurement,this expanded state can be one that the stent will self-expand to withina straight glass cylindrical tube with an inside diameter that issmaller than the maximum diameter to which the stent will self-expand inthe absence of any containment or external forces.) In some embodiments,the average pore size can be less than about 320 microns. Indeed,because of such exceedingly small average pore sizes, any known priordevice or attempt at manufacturing such a device resulted in substantialwebbing, delamination, and uneven application of coating to the device.In contrast, some embodiments disclosed herein enable and provide adevice and methods of manufacturing in which the device has a flowdiverting section that is substantially free of webbing, delamination,and other coating deficiencies.

Accordingly, some embodiments provide a device, such as a braided stent,that can have a flow diverting section or other portion of the devicethat provides embolic properties so as to interfere with blood flow in(or into) the body space (e.g., an aneurysm) in (or across) which thedevice is deployed. The porosity and/or pore size of one or moresections of the device can be selected to interfere with blood flow to adegree sufficient to thrombose the aneurysm or other body space.

For example, some embodiments provide a device (e.g., stent) that can beconfigured to interfere with blood flow to generally reduce the exchangeof blood between the parent vessel and an aneurysm, which can inducethrombosis of the aneurysm. A device (or a device component, such as asidewall of a stent or a section of such a sidewall) that thusinterferes with blood flow can be said to have a “flow diverting”property.

Additionally, in some embodiments, a device (e.g., stent) can beprovided with a porosity in the range of 5%-95% may be employed in theexpanded braid. In some embodiments, a porosity in the range of 30%-90%may be employed. Further, a porosity in the range of 50%-85% may beemployed.

Further, in some embodiments, a device (e.g., stent) can be providedwith a pore size in the range of 20-300 microns (inscribed diameter). Insome embodiments, a pore size in the range of 25-250 microns (inscribeddiameter) may be employed. In some embodiments, a pore size in the rangeof 50-200 microns (inscribed diameter) may be employed.

Methods of treatment and methods of manufacturing embodiments of thedevices (e.g., stents) disclosed herein are also provided. Therefore,various embodiments of the devices disclosed herein address the problemsand complications associated with unevenly and improperly coated devices(e.g., stents) and provide novel processes for manufacturing and usingsuch devices.

Some embodiments of processes disclosed herein comprise mounting ormaintaining a braided device (e.g., stent) in a longitudinally stretchedconfiguration during the coating process. Such a device can have anexpanded configuration in which the pores thereof are generallycircumferentially elongated, which results in a decreased pore size or arelatively “closed” configuration. In contrast, the pore size isincreased or in a relatively “open” configuration when the device is inthe longitudinally stretched configuration. In the longitudinallystretched configuration, many, if not all, of the pores of the devicecan be opened to an enlarged pore size, or to a generally maximum poresize.

For example, in some embodiments, the longitudinally stretchedconfiguration can open the pores by orienting the individual filamentsof the device to create a pattern of open-pore quadrilaterals, such assquares, rectangles, parallelograms, rhombuses, trapezoids, etc., whichcan allow the pore size to be generally maximized. Further, thequadrilaterals can be formed by filaments that cross at angles fromabout 0° to about 15° from a right angle. In some embodiments, theangles can be from about 0° to about 10° from a right angle. In someembodiments, the angles can be from about 0° to about 5° from a rightangle. Additionally, in some embodiments, the filaments can formright-angled quadrilaterals, such as squares and rectangles, whichallows the pore size to be maximized. However, not every pore shapecircumscribed by the filaments may be a right-angled quadrilateral, andsome variation between pores in the same or different sections of adevice is possible.

Further, some embodiments of processes disclosed herein comprise dippinga longitudinally stretched braided device (e.g., stent) in a solvent andthereafter “air knifing” the dipped device to remove or blow off anyexcess solvent from the device. The air jet(s) of the air knife(s) canbe applied in a direction that is generally transverse, such asorthogonal, relative to the longitudinal axis of the device. The airknife can be stationary while the device is moved, or it can move alongor about the device as the device remains stationary.

Additionally, some embodiments also provide a coating fixture which canbe used during the coating (e.g., dipping, spraying, etc.) processes tooptimize the coating and drying process and prevent inadvertent wickingof the coating material away from the coated device (e.g. stent), whichcan result from undesired contact with the coated device (e.g., stent)during the process. Some embodiments of the coating fixture can be bothrigid and/or lightweight. Further, in some embodiments, the coatingfixture can comprise first and second ends that engage withcorresponding ends of the device and a fixture body that extends betweenthe first and second ends and outside of a device lumen when the deviceis mounted to the fixture. The first and second ends can be spaced apartsufficiently to maintain the device in a longitudinally stretchedconfiguration when mounted on the cantilevered fixture.

The device (e.g., stent) can take the form of a vascular occludingdevice, a revascularization device and/or an embolization device. Insome embodiments, the device can be an expandable stent made of two ormore filaments. The filaments can be formed of known flexible materialsincluding shape memory materials, such as nitinol, platinum andstainless steel. In some embodiments, the filaments can be round orovoid wire. Further, the filaments can be configured such that thedevice is self-expanding. In some embodiments, the device can befabricated from a first group of filaments made of platinum alloyed with8% tungsten, and a second group of filaments made of 35N LT (cobaltnickel alloy, which is a low titanium version of MP35N alloy). In otherembodiments, one or more of the filaments can be formed of abiocompatible metal material or a biocompatible polymer.

The wires or filaments can be braided into a resulting lattice-likestructure. In at least one embodiment, during braiding or winding of thedevice (e.g., stent), the filaments can be braided using a1-over-2-under-2 pattern. In other embodiments, however, other methodsof braiding can be followed, without departing from the scope of thedisclosure. The device can exhibit a porosity configured to reducehaemodynamic flow into and/or induce thrombosis within, for example, ananeurysm, but simultaneously allow perfusion to an adjacent branchvessel whose ostium is crossed by a portion of the device. As will beappreciated, the porosity of the device can be adjusted by “packing” thedevice during deployment, as known in the art. The ends of the devicecan be cut to length and therefore remain free for radial expansion andcontraction. The device can exhibit a high degree of flexibility due tothe materials used, the density (i.e., the porosity) of the filaments,and the fact that the ends of the wires or filaments are not secured toeach other.

Information regarding additional embodiments, features, and otherdetails of the devices, methods of use, and other components that canoptionally be used or implemented in embodiments of the occlusiondevices described herein, can be found in Applicants' co-pending U.S.patent application Ser. No. 12/751,997, filed on Mar. 31, 2010; Ser. No.12/426,560, filed on Apr. 20, 2009; Ser. No. 11/136,395, filed May 25,2005; Ser. No. 11/420,025, filed May 24, 2006; Ser. No. 11/420,027,filed May 24, 2006; Ser. No. 12/425,604, filed Apr. 17, 2009; Ser. No.12/896,707, filed Oct. 1, 2010; 61/483,615, filed May 6, 2011;61/615,183, filed Mar. 23, 2012; Ser. No. 13/614,349, titled Methods andApparatus for Luminal Stenting, filed on Sep. 13, 2012 (referenceHKN-02608 (1), 080373-0366); Ser. No. 13/692,021, titled Methods andApparatus for Luminal Stenting, filed on Dec. 3, 2012 (referenceHKN-02608 (2), 080373-0377); and Ser. No. 13/664,547, titled Methods andApparatus for Luminal Stenting, filed on Oct. 31, 2012 (referenceHKN-02608 (3), 080373-0498); the entireties of each of which areincorporated herein by reference.

FIG. 4 illustrates a tubular, self-expanding device, shown as a stent100, comprising a coating 110 disposed along at least a portion thereof.The tubular stent 100 comprises an elongate hollow body which can beformed from a plurality of braided filaments. Some embodiments disclosedherein can comprise a coating along the entire length of the stent ormerely along only a portion thereof. The stent 100 can comprise a flowdiverting portion 112. The flow diverting portion 112 can comprise aplurality of pores that have a flow diverting pore size; instead of orin addition to this property, the flow diverting portion 112 can have aflow diverting porosity. The flow diverting portion 112 can comprise aportion of the stent 100, or the entire stent. The flow diverting poresize can be an average pore size within a relevant portion of the stent,e.g. within the flow diverting portion 112 or a portion thereof, or a“computed” pore size, one that is computed from measured or nominalbasic stent parameters such as braid angle, number of filaments,filament size, filament diameter, stent diameter, longitudinal picks perinch, radial picks per inch, etc. Such a computed pore size can beconsidered to be one type of average pore size. The flow diverting poresize can be within a size range that that interferes with or inhibitsblood flow through the sidewall of the stent 100, for example, betweenthe parent vessel and an aneurysm sufficient to induce or lead tothrombosis of the aneurysm. The coating can be disposed partially orentirely along the flow diverting portion 112, or along another portionof the stent 100.

In some embodiments, the pores of the flow diverting portion 112 canhave an average pore size of less than 500 microns (inscribed diameter),or in the range of 20-300 microns (inscribed diameter). Further, theaverage pore size can be in the range of 25-250 microns (inscribeddiameter). Furthermore, the average pore size can be in the range of50-200 microns (inscribed diameter). The stent 100 can be expandablefrom an unexpanded diameter to an expanded diameter; the unexpandeddiameter can optionally be 5 mm or less, or 4 mm or less, or 3 mm orless, or 2 mm or less, or other unexpanded diameters, and/or theexpanded diameter can optionally be 2 mm or more, or 3 mm or more, or 4mm or more, or 5 mm or more, or other expanded diameters. The unexpandeddiameter can be less than the expanded diameter.

The average pore size of the pores in the flow diverting portion 112 canbe the average size of the pores measured with or without coatingmaterial disposed thereon. Thus, the average pore size of the flowdiverting portion of a bare stent can be within the flow divertingranges. Further, the average pore size of the flow diverting portion ofa coated stent can be within the flow diverting ranges. Furthermore, theflow diverting portion 112 can comprise pores having sizes above orbelow the range of the average pore size.

FIG. 5A illustrates an enlarged view of a section of the flow divertingportion 112 of the stent 100. In this embodiment, the flow divertingportion 112 comprises a plurality of filaments 120 that are braidedtogether to form the tubular body of the stent 100. FIG. 5A illustratesthe self-expanding stent 100 in an expanded or relaxed state. In thisexpanded or relaxed state, the filaments 120 cross each other to formthe pores of the stent 100.

FIG. 5B illustrates a single pore 140 of the flow diverting section 112when in the relaxed state. The pore 140 is formed by a plurality offilaments 142, 144, 146, and 148. As shown, the filaments 142, 144 crosseach other to form an obtuse angle 150. In some embodiments, the obtuseangle 150 can be from about 110° to about 170°. Further, the obtuseangle 150 can be from about 120° to about 165°. Further, the obtuseangle 150 can be from about 130° to about 160°, and in some embodiments,the obtuse angle 150 can be about 150°.

Accordingly, the size or configuration of the pore 140 is “closed” orrelatively small in the expanded or relaxed state shown in FIG. 5B whencompared with the relatively “open” size of the pore 140 when the stent100 is in a longitudinally stretched configuration, as shown in FIG. 5C.FIG. 5C illustrates that the filaments 142, 144, 146, and 148 each crosseach other at angles 160 that approximate a right angle, e.g. withinfrom about 0° to about 15° from a right angle. In some embodiments, theangles 160 can be from about 0° to about 10° from a right angle. In someembodiments, the angles 160 can be from about 0° to about 5° from aright angle.

Additionally, in order to maximize the pore size, in some embodiments,the filaments can form right-angled quadrilaterals, such as squaresand/or rectangles. However, not every pore shape circumscribed by thefilaments may be a right-angled quadrilateral, and some variationbetween pores in the same or different sections of a stent is possible.

A device can be prepared according to some embodiments by braiding aplurality of filaments to form a braided stent, filter, or other braideddevice. The device can then be cleaned and heat treated, if necessary,to impart desired characteristics to the device. Thereafter, the devicecan be coated using aspects of the methods disclosed herein.

FIGS. 6-12 illustrate aspects of a coating apparatus and method that canbe used in some embodiments to coat the stent 100, or any otherembodiments of stents or other devices disclosed herein. FIG. 6illustrates a coating system 170 that generally comprises a handlingsystem 180, a mounting apparatus 210 that is held by the handling system180 and in turn holds the stent 202, an open-topped container (e.g., abeaker) of coating solution 260, and an air knife 270.

The handling system 180 is generally configured to rotate and move thestent 202 and mounting apparatus 210 vertically up and down. Thus thehandling system 170 includes a powered linear actuator 172 that isoriented vertically and further includes a carriage 174 that can move upand down on, and under the power of, the linear actuator 172. On thecarriage 174 is mounted an electric motor 176; when powered the motor176 rotates a chuck 178. The chuck 178 detachably grips an upper end ofthe mounting apparatus 210 so that the motor 176 rotates the mountingapparatus 210 and stent 202 about a generally vertical axis when themotor 176 is energized.

The coating solution 260 is positioned beneath the motor 176 andmounting apparatus 210, and aligned generally with the mountingapparatus 210 and the rotational axis of the motor 176. Therefore, adownward movement of the carriage 174 (and with it the motor 176 andmounting apparatus 210) along the linear actuator 172 will cause thelower portions of the mounting apparatus 210 and stent 202 to beimmersed in the coating solution 260 (see FIGS. 7A, 7B).

The air knife 270 comprises a nozzle 271 that is connected via a hose toa source of pressurized air or other pressurized gas (not shown). Thenozzle 271 is positioned and oriented so that, upon activation of theair knife 270, the nozzle directs an air jet or air stream 272 (see FIG.8B) that strikes the stent 202 when the carriage 174 and motor 176 arepositioned along or moving through a particular “air knifing” region ofthe linear actuator 172.

The coating system 170 can be used to coat a stent generally as follows.The process begins with the coating system in the start position shownin FIG. 6. The linear actuator 172 is energized to lower the carriage174, and with it the motor 176, mounting apparatus 210 and stent 202,until the lower portions of the apparatus 210 and stent 202 aresubmerged in the coating solution 260 (see FIGS. 7A, 7B). The mountingapparatus 210 and stent 202 are left in the solution 260 momentarilybefore the linear actuator 172 is energized again to raise the stent202, now wet with coating solution, toward the air knife 270. When thestent 202 is fully out of the coating solution 260, the actuator 172pauses for a brief pre-drying period before moving the stent 202 intothe air stream 272. Once the pre-drying period is over, the stent ismoved upward into the air stream 272. While the air stream 272 isstriking the stent 202, the stent is simultaneously rotated andreciprocated vertically (via the motor 176 and actuator 172,respectively) relative to the nozzle 271 so that the stent is moved backand forth through the air stream. Thus, substantially all of the outersurface of the stent 202 is moved across the nozzle 271 and exposed tothe air stream 272 during the knifing process, and any excess coatingsolution is blown off.

After air knifing is complete, the stent 202 is then raised out of thestream 272 via the actuator 172 (and/or the air knife 270 isdeactivated), as shown for example in FIG. 9A. The mounting apparatus210 is now removed from the motor 176 by loosening the chuck 178. Thestent 202 can be allowed to dry further while still mounted on themounting apparatus, either at room temperature or at elevatedtemperature in a drying oven. Once the stent is dry, it can be removedfrom the mounting apparatus 210 and cut to its final length by trimmingoff one or both ends of the stent.

More specific aspects of the coating system 170 and methods of coatingwill now be discussed in greater detail.

Enlarged views of the mounting apparatus 210, with the stent 202 mountedthereon, are illustrated in FIGS. 10-12. The stent 202 comprises atubular braid (which can be similar to any of the herein-describedembodiments of the stent 100), with an upper portion 204 and a lowerportion 206. As shown in FIGS. 10-11, in order to facilitate attachmentto the mounting apparatus 210, the stent upper portion 204 can be closedand comprise an elongate wire 208 that extends therefrom. For example,in some embodiments, wire 208 can be welded to the stent upper portion204 to close the stent 202 and form a cone at its upper portion 204. Theelongate wire 208 can be engaged by an upper fixture 220 of the mountingapparatus 210. The upper fixture 220 can comprise an alligator clip thatcan grip the wire 208, or a hook or pin around which the wire 208 can bewound, or other mechanical fastener operative to securely engage thewire 208.

Further, as shown in FIGS. 10 and 12, the stent lower portion 206 cancomprise an open end. The stent lower portion 206 can be engaged by alower fixture 222 of the mounting apparatus 210. The lower fixture 222can comprise an alligator clip, a hook, or other mechanical fasteneroperative to securely engage the stent lower portion 206. For example,FIG. 12 illustrates a pair of deflectable prongs that can be insertedinto a lumen of the stent 202 and exert a biasing force such that endsof the deflectable prongs engage the inner wall of the stent lowerportion 206. Each prong includes near its upper tip an outwardly- anddownwardly-projecting barb 223 (FIG. 9D) that is received in andprojects through a pore of the stent 200, to facilitate a secure grip ofthe lower portion 206.

The mounting apparatus 210 (see also FIGS. 9B-9D) can comprise anelongate backbone 240 that interconnects the upper and lower fixtures220, 222. The upper and lower fixtures 220, 222 can define an axis 242extending therebetween, along which an axis of the stent 200 can begenerally aligned when mounted on the fixtures 220, 222. The elongatebackbone 240 can comprise a relatively thin, but nonethelesssufficiently rigid, wire, for example a single stainless steel wire of0.055 inch diameter.

The depicted mounting apparatus 210 incorporates a number of designfeatures that enable high-precision coating of the stent 100/202. Theupper and lower fixtures 220, 222 are spaced apart so that the stent isheld in a longitudinally stretched configuration and the pores arecaused to take on the “open” configuration shown in FIG. 5C,characterized by the formation of approximately right angles between thefilaments. With the pores so opened, any webs can be blown out of thepores without need for a high-pressure air stream which presents a riskof blowing too much of the coating solution off the stent. Substantiallyno portion of the mounting apparatus 210 protrudes into the lumen of thestent (the sole exception being the tips of the prongs of the lowerfixture 222, which extend into a portion of the stent that will betrimmed away after coating is complete). As a result, the mountingapparatus does not interfere with the flow of the air stream 272 throughthe stent during the knifing process. The only portion of the mountingapparatus 210 that is ever situated between the nozzle 271 and the stentduring the knifing process is the backbone 240. However, the effect ofthis is mitigated by (1) the narrow, thin profile of the backbone 240,(2) the offset between the backbone 240 and the stent, which allows theportion of the stent that is “shadowed” by the backbone to be impactedeffectively by the air stream 272 immediately before and after thebackbone passes through the air stream, and (3) the fact that thebackbone 240 interrupts the air stream 272 only momentarily, once perrevolution of the stent, as opposed to the constant airflow interruptionthat would result from an apparatus member that extends through thestent lumen. The absence of any mounting apparatus member 210 in thestent lumen, and the offset between the backbone 240 and the stent,further contribute to precision coating by reducing or eliminating thepossibility of the stent contacting the backbone 240 or anyluminally-protruding apparatus member as the stent deflects in reactionto air stream 272 striking the stent. Such contact can wick coatingsolution away from the stent and degrade the quality of the resultingcoating. The tension induced in the stent by virtue of beinglongitudinally stretched in the mounting apparatus 210 also assists inreducing/eliminating such undesired contact resulting from deflection ofthe stent. The configuration of the mounting apparatus 210 substantiallyaligns the axis 242, which is approximately the axis of rotation of theapparatus 210 and the stent when the knifing process is underway, withthe central longitudinal axis of the stent. Accordingly, the stent isrotated substantially “on center” during the knifing process, whichhelps promote an even distance between the stent and the nozzle 271 (andeven application of the air stream 272 to the stent) through 360 degreesof rotation of the stent. In addition, the configuration of the lowerfixture 222 “places” minimal weight of the mounting apparatus 210 in alocation remote from the point of attachment of the apparatus 210 to thechuck 178. It was found that using a clip-and-wire arrangement similarto the upper fixture 220 and upper portion 204 placed too much weighttoo far from the chuck 178, which induced a “pendulum effect” in themounting apparatus 210 in reaction to the incident air stream 272, asthe apparatus 210 deflected off axis and the resulting back-and-forthmotion of the apparatus 210 was magnified by the mass of the relativelyheavy lower fixture and its location a relatively long distance awayfrom the chuck 178. A large pendulum effect pulls the stent off-centerduring knifing and results in uneven application of the air stream 272to the stent. In comparison, the lighter weight and shorter length ofthe lower fixture 222 employed in the depicted mounting apparatus 210reduces the pendulum effect to acceptable levels or eliminates italtogether. The relatively thin profile of the members constituting themounting apparatus (particularly the backbone 240) also reduces thependulum effect by reducing the force of the air stream 272 impinging onthe mounting apparatus. The depicted lower fixture 222 also keeps thelower portion 206 of the stent open, which allows for more effectivedraining of excess coating solution from the stent after the stent hasbeen raised out of the coating solution 260, as compared to the conicalconfiguration of the stent upper end 204 employed with the upper fixture220. The overall cantilevered configuration of the mounting apparatus210 facilitates dipping the stent in the coating solution 260, andsubsequently raising the stent toward the air knife 270 in a simplestraight line, while incorporating a brief pre-drying pause before theknifing process begins.

As illustrated in the enlarged view of the dipping procedure shown inFIG. 7B, the stent 202 is lowered into the coating solution 260 untilthe stent upper portion 204 reaches the top surface 262 of the coatingmaterial 260, but the stent upper portion 204 is not submersed into thecoating material 260. Accordingly, the conical upper portion 204 remainsdry. The Applicants discovered that, when the conical upper portion isleft dry and uncoated, the coating solution drains more effectively fromthe stent after it is raised out of the solution 260. This moreeffective draining of the solution in turn facilitates a neater, moreprecise blow-off of the solution from the stent and better coatingperformance.

In a preferred embodiment of the above-described method and apparatusfor coating a stent, the dimensions and process parameters shown inTable 1 below can be used for constructing the mounting apparatus 210and performing the method.

TABLE 1 Mounting Apparatus Dimensions (FIGS. 9B, 9C, 9D) ProcessParameters Dimension Size Parameter Value A 6.5″ Air knife pressure 12PSI B 0.56″ Air knife flow rate Approx. 26 SLPM C 0.7″ Distance fromnozzle to stent 60 mm D 1.25″ Nozzle inside diameter 2.0 mm E 2.9″Rotation speed 100 RPM F 2.5″ Reciprocation speed 24 mm/s G 0.5″Reciprocation: number of passes 5 through air stream H 0.055″ (wirediameter) Amount of longitudinal stretch of Approx. 2x stent, from restI 0.353″ Stent braid angle when stretched Approx. 90 degrees J 10degrees Pre-drying time 10-15 seconds K 1.0″ Drying temperature 60degrees C. L 0.032″ (diameter) Drying time 15 minutes Process ambienttemperature and Room temperature humidity and humidity Coating solutiontemperature Room temperature Pressurized air source Standard “shop” airwith in-line air dryer

Some of these parameters can be varied in other embodiments. Forexample, the air knife pressure could be 6-18 PSI, or 10-14 PSI; thedistance from the nozzle to the stent could be 20-80 mm, or 40-70 mm;the stent rotation speed could be 50-150 RPM, or 80-120 RPM; thereciprocation speed could be 10-40 mm/s, or 18-30 mm/s; the amount oflongitudinal stretch of the stent could be 1.5×-3×; the dryingtemperature could be 50-80 degrees C.; and/or the drying time could be5-60 minutes. Although the air knife 270 is described as blowing air onthe stent, other gases could be employed, such as nitrogen, argon orother relatively inert gases.

Other variations of the method and apparatus are possible. For example,multiple nozzles or gas sources could be used in the air knife 270instead of the single nozzle 271 depicted and described above. The airknife 270 can move during the knifing process while the stent 202remains stationary, rather than the reverse as described above. Thebackbone 240 can be made in a constant thickness or diameter that variessomewhat from that specified herein, or the backbone 240 can taper. Forexample, the backbone 240 can taper from a larger size at its upper endto a smaller size at its lower end.

Further, although dip coating and removal of excess coating material byair knife are discussed above, other coating methods can be implemented.For example, in some embodiments, the stent can be coated using a spraycoating process. In spray coating, the coating material may be appliedto the device using a spray coater.

Referring now to FIG. 13, an enlarged view of the stent 204 is shown inits longitudinally stretched configuration, as achieved when engaged bythe mounting apparatus 210 during the coating process. As illustrated,the stent 204 comprises a plurality of filaments 300. Each of theillustrated filaments 300 has been dipped in the coating material and anair stream has been applied to remove excess coating material from thefilaments 300. The coating material thus remaining extends only alongthe filaments 300, without any webbing or delamination occurring.

In this embodiment, the filaments 300 cross each other in a generallyorthogonal orientation relative to each other. As illustrated, thefilaments 300 cross each other at angles of from about 75° to about105°, or within from about 0° to about 15° from a right angle.

Generally, according to aspects of embodiments disclosed herein, whenthe filaments cross each other at substantially orthogonal or rightangles (e.g., within about 15° from a right angle), the inter-filamentspace or crevice area (e.g., the gaps formed between surfaces ofoverlapping filaments at their crossing point) is minimized, thusreducing the space in which coating material can accumulate in excess ofwhat is required to coat the filament surface. For example, an aspect ofembodiments disclosed herein is the realization that the coating may bethicker in inter-filament spaces or crevices due to the surface tensionof the coating material. Thus, reducing the inter-filament space canalso reduce the amount of coating material captured therein by virtue ofthe coating material surface tension.

For example, FIGS. 14A-B illustrate an embodiment of a stent 320 inwhich filaments 322, 324 overlap at a crossing point 326. FIG. 14A showsa coating that demonstrates excellent uniformity, smoothness, and issubstantially free of webbing. The filaments 322, 324, which aregenerally cylindrical, generally have a single contact point 330. Due tothe contact and overlap between the filaments 322, 324, aninter-filament or crevice area 332 is formed immediately adjacent to thesingle contact point 330. During the coating process, excess coatingmaterial can accumulate in the crevice areas 332, which can be difficultto remove. However, according to embodiments disclosed herein, thepresence and size of inter-filament or crevice areas throughout thebraided stent can be minimized by ensuring that the filaments of theportion of the stent to be coated are oriented substantiallyorthogonally relative to each other. Thus, in some embodiments, athickness of a coating 350 disposed on the filaments 322, 324 can have agenerally constant thickness, even along the crevice areas 332. Further,even with some coating material accumulation, the thickness of thecoating 350 disposed in the crevice areas can be less than twice thethickness of the coating 350 disposed on the filaments 322, 324.

Some embodiments of the devices and methods disclosed herein cantherefore provide a device, such as a stent or a braided stent, having acoating that is substantially free of webs, and in some embodiments,that also has a flow diverting pore size and/or a flow divertingporosity that is/are exhibited throughout the entire stent, or in a flowdiverting portion or section of the stent. In one embodiment, a coateddevice, stent or section is “substantially free” of webs when any websthat are present are sufficiently few in number so as to not interferewith the function of the device. Alternatively, a coated device, stentor section that is substantially free of webs can be one in which thereis webbing present at fewer than 5% of the filament crossing points,and/or at fewer than 5% of the pores. In another alternative, a coateddevice, stent or section that is substantially free of webs can be onein which there is webbing present at fewer than 3% of the filamentcrossing points, and/or at fewer than 3% of the pores. As yet anotheralternative, a coated device, stent or section can have no webbing atall in any of the filament crossing points, and/or in any of the pores.

Instead of or in addition to the substantial or complete absence ofwebbing discussed above, the coating of the device, stent or section canbe substantially complete. Substantial completeness of coverage can beachieved when the filaments are covered completely along their lengthwithin the device, stent or section, with the exception of (a) uncoatedareas amounting to less than 5%, or less than 3%, of the outer surfaceof the filaments, and/or (b) uncoated and/or less-coated (e.g. withfewer than all layers of a multi-layer coating) areas in some or all ofthe filament crossing points. Alternatively, the coated device, stent orsection can be completely coated.

Instead of or in addition to the properties described above relating tolack of webs and/or completeness of coverage, the device, stent orsection can be coated with an antithrombogenic coating sufficiently toreduce the thrombogenicity of the coated stent, device, section, etc. ascompared to a similar but uncoated stent, device, section, etc. Thereduction in thrombogenicity can be significant. Stents coated accordingto the method disclosed herein have been tested for increasedantithrombogenicity via thrombogram, employing the following assay.

Materials Description Information/Purpose Source Human Platelet 240 mLstock of citrated aphorized Red Cross, Dedham, MA Packs human plateletsin plasma (PRP) Fluorogenic For thrombin detection (Z-Gly-Gly- BachemAmericas, Inc., substrate Arg-AMC-HCl, 40 mM stock in Torrance, CAdimethyl sulfoxide) Cat#: I-1140 Calcium Chloride For startingcoagulation and thrombin Sigma Aldrich Corp., St. Louis, (CaCl₂)generation (1M stock in Distilled MO Water) Cat#: 223506-2.5 KG 4 mmGlass Positive control for thrombin Fisher Scientific, Waltham, MASpheres generation (assay only) Cat#: 11-312B Sodium Storage of samplespost-testing; Clorox Co., Oakland, CA Hypochlorite Cleaning of glassspheres pre-testing Thrombin For calibration (RFU to Thrombin) inDiagnostica Stago, Inc., Calibrator autologous PPP Parsippany, NJ Cat#:TS20.00, 1 mL vials HEPES Buffered For preparation of and serialdilutions Sigma Aldrich Saline of Thrombin stock for calibration Cat#:51558-50 ML Dimethyl Sulfoxide For substrate stock solution SigmaAldrich (25 mg/mL) Cat#: D8418-100 ML 50 mL Reagent For loading samplesolutions into Fisher Scientific Reservoir Multipipette DispenserPolystyrene Centrifuge For obtaining platelet poor plasma EppendorfNorth America, (PPP) from PRP Hauppauge, NY 5810R Rocker For storing PRPbags until use Fisher Scientific Labline OptiPlate For assayingfluorescence of multiple Fisher Scientific black/opaque 96- test samplesand controls well microplate Synergy HT Plate For simultaneous kineticfluorescence Biotek Instruments, Inc., Reader measurements of multiplesamples Winooski, VT Particle Counter For platelet counts (final countsin Beckman Coulter, Inc., Brea, plasma as required) CA Multipipette Forsimultaneously dispensing reagents Mettler Toledo, Inc., Columbus,Dispenser into multiple microplate wells OH Rainin Ruler/CalipersDimensions of test samples MSC Balance For weighing of stent piecesMettler Toledo

The citrated stock (˜240 ml) of platelet rich plasma (PRP) was stored onthe rocker (setting: 2) at room temperature for 3 days (up to a maximumof 1 day post printed expiration date). PPP (platelet poor plasma) wasprepared on day 1 of obtaining the corresponding PRP stock, as follows:(a) pour 100 mL of PRP stock suspension into two 50 mL centrifuge tubes;(b) centrifuge for 30 minutes at 2900×g; (c) carefully pour out thesupernatant-platelet poor plasma (PPP) and filter it using a 0.22 μmsyringe-driven filter unit; (d) divide some of the PPP into 5 mLaliquots; (e) store the PPP aliquots at −80° C.; and (e) utilize 50 mLof PPP for dilution of autologous PRP for purposes of the assay.

Next, Diluted PRP was prepared as follows: (a) perform platelet count(counting particles within size range of 2 μm-4 μm for PRP stocksolution) in the particle counter by priming the aperture and cleaningthe apparatus with purified water, diluting 10 μL of PRP stock in 10 mLof electrolyte solution and initiating the count, and recording the meanplatelet count of the PRP stock; (b) dilute PRP to a final count of200,000 per μL with autologous PPP; and (c) calculate total volume ofPRP and PPP needed for assay (per sample=250 μL).

Samples of stents that were coated according to the method disclosedherein (“test stents”) and of identical but bare-metal stents (“barestents”) were prepared as follows: (a) cut sections of each stent to alength of 9 mm; (b) immerse the sections individually in a 1.5 mLcentrifuge tube filled with deionized water for 30 minutes; and (c)after wetting, blot out the excess water from each stent section on akimwipe.

The 96-well microplate was then loaded with the following: (a) teststent sections (5 wells); (b) bare stent sections (5 wells); (c) 4 mmglass spheres (5 wells, to function as a positive control); and (d)blanks (5 wells with no samples, serving as a negative control). Onlyone of a test stent section, bare stent section or glass sphere wasplaced in any one well. The plate reader was then turned on and allowedto warm up for three minutes, while the associated PC software (Gen 5)was launched. The settings used were: test temperature 25° C.;fluorescence reading (excitation (nm): 360/40, emission (nm): 460/40);no shake; kinetic reading every one minute for each well; totalexperimental time of two hours. Generally, the plate reader was set upfor immediate read before preparing the test solutions.

Test solutions were prepared immediately before the analysis as follows.Experimental solution was prepared by adding fluorogenic substrate (25mg/mL) (40 mM) to Diluted PRP (final count 200,000/μL) in a 15 mLcentrifuge tube for a final concentration of 400 μM, then adding 1Mcalcium chloride for a final concentration of 20 mM, and inverting thetube to mix. Calibrator solutions were prepared by (a) adding 1 mL ofdeionized water to a 1 mL vial (as packaged) of the lyophilized thrombincalibrator; (b) preparing 10 mL of HBS-BSA solution (20 mM HEPES, 10mg/ml bovine serum albumin (BSA), pH 7.4, filtered with the 0.22 μmsyringe filter); (c) making four serial dilutions of the calibrator asprepared in step (a), in HBS-BSA (1:2, 1:20, 1:200, 1:2000); (d) adding100 μL of the fluorogenic substrate to 10 mL of PPP; and (e) mixing fivecalibrator solutions as follows: (1) by mixing fourteen parts of thesubstrate-PPP mixture of step (d) with one part of the 1:2 dilution ofstep (c); (2) by mixing fourteen parts of the substrate-PPP mixture ofstep (d) with one part of the 1:20 dilution of step (c); (3) by mixingfourteen parts of the substrate-PPP mixture of step (d) with one part ofthe 1:200 dilution of step (c); (4) by mixing fourteen parts of thesubstrate-PPP mixture of step (d) with one part of the 1:2000 dilutionof step (c); and (5) by mixing fourteen parts of the substrate-PPPmixture of step (d) with one part of the (undiluted) calibrator asprepared in step (a).

The test solutions were transferred to the microplate as follows: (a)300 μL of the experimental solution in each of the wells containing atest stent section, a bare stent section, or a glass sphere, and in eachof the five designated blanks; and (b) 300 μL of calibrator solution ineach of ten wells containing no sample (separate from the blank wells),two wells each for each of the five calibrator solutions describedabove. A multipipette dispenser was used for the experimental solutionto ensure that all wells were filled in less than one minute.

The microplate was then placed the reader and the test was run. Thecoated stents were found to result in a significant delay in peakthrombin formation, as compared to a similar but uncoated stent. Inparticular, the elapsed time before peak thrombin formation was found tobe about 2.5 times that of the similar but uncoated stent. In anotherexperimental run, the elapsed time before peak thrombin formation wasfound to be about 1.5 times that of the similar but uncoated stent.Accordingly, the time before peak thrombin formation with the coateddevice, stent, section, etc. can be more than 1.5 times, or more thantwice, or about 2.5 times, or about 1.5 times that of a similar butuncoated device, stent, section, etc.

The substantial or complete absence of webbing in the coated device,stent, section, etc. can be observed in SEM (scanning electronmicroscope) imaging. FIGS. 16A-19C are SEM images of four differentbraided stents that were coated using the process disclosed herein andaccording to the parameters shown in Table 1, each at three levels ofmagnification: 50× (the “A” images), 150× (the “B” images), and 500×(the “C” images). No webbing can be observed in any of these images.From observation of the images, the pore size of the stent shown inFIGS. 16C and 19C, as measured by the diameter of an inscribed circlewithin the pore, is approximately 110 microns. The pore size of thepores illustrated in FIGS. 17C and 18C is approximately 80 microns.

FIGS. 16A-19C also show complete coverage of the coated stents.Completeness or substantial completeness of coverage, as well as coatinguniformity, can also be observed from weight-gain data obtained fromcoated stents. FIG. 15 depicts the results of a weight-gain studyperformed on six stents that were coated with the process disclosedherein and according to the parameters shown in Table 1. After coating,each stent was cut into four equal-length longitudinal sections(Proximal, Middle #1, Middle #2 and Distal) that were weighed separatelyto compute a percent weight gain for each stent section. (The bareweight of each section was determined as ¼ of the pre-coating weight ofthe stent.) As can be seen in FIG. 15, the percent weight gain washighly consistent across all the 24 stent sections. These data indicatecompleteness or substantial completeness of coverage, as well asuniformity of coverage, because a process that generates piecemeal orgap-laden coverage would be expected to result in high variance inweight gain among the measured sections.

Accordingly, instead of or in addition to the other coating propertiesdiscussed herein, the device, stent or section can have a coating weightgain in each of four longitudinal sections of the device, stent orsection, wherein the weight gain varies by no more than 2.5 percentagepoints, or no more than 4 percentage points, or no more than 5percentage points, between the largest and smallest gains among the foursections.

Example 1

Braided tubular stents were coated according to the process describedherein and the parameters provided in Table 1. Each of the stents wasconfigured as follows: 48 braided filaments, of which 12 were ofplatinum alloyed with 8% tungsten, with 0.0012 inch filament diameter,12 were of 35NLT, with 0.0012 inch filament diameter, and 24 were of35NLT, with 0.0014 inch filament diameter; overall outside diameter 5.2mm and longitudinal picks per inch of 275, both dimensions prevailingwhen in an expanded, unconstrained and unstretched condition.

The stents were provided in their “bare metal” condition, and preparedas follows. First, they were washed in 99.5% acetone for five minutes inan ultrasonic cleaner, and then washed in 99% isopropyl alcohol (IPA) inan ultrasonic cleaner, in two separate five-minute IPA wash stages.After washing, the stents were rinsed in distilled water and then driedin an oven at 60 degrees C. for 30 minutes.

A coating solution of 2-Methacryloyloxyethyl phosphorylcholine (MPC) wasprepared by dissolving 2.0 grams of MPC (LIPIDURE™-CM2056) in 200milliliters of ethanol, and provided in a beaker at room temperature.The coating process was then performed on each of the stents, accordingto the description provided herein and the parameters shown in Table 1.After completion of the process and trimming, the stents could bedescribed as tubular braided stents, open at each end with a lumenextending from one end to the other, and with a coating of MPC over theentirety of the stent filaments.

FIGS. 16A-19C are SEM images of four stents coated according to thisExample 1. As described previously, the images indicate that the stentsare coated completely and with no observable webbing in the pores.

FIG. 15 depicts the results of a weight gain study performed on sixstents coated according to this Example 1. Again, the weight-gain datashows that the stents were coated completely or substantiallycompletely, and with high uniformity.

Stents coated according to this Example 1 were tested for increasedantithrombogenicity via thrombogram, employing the assay describedabove. The coated stents were found to result in a significant delay inpeak thrombin formation, as compared to an identical but uncoated stent.In particular, the elapsed time before peak thrombin formation was foundto be about 2.5 times the time observed with the identical but uncoatedstent.

Methods of Treatment

As mentioned elsewhere herein, the present disclosure also includesmethods of treating a vascular condition, such as an aneurysm orintracranial aneurysm, with any of the embodiments of the coated stentsdisclosed herein. The coated, low-thrombogenicity stent could bedeployed across the neck of an aneurysm and its flow-divertingproperties employed to reduce blood flow between the aneurysm and theparent vessel, cause the blood inside the aneurysm to thrombose and leadto healing of the aneurysm.

Significantly, the low-thrombogenicity stents disclosed herein canfacilitate treatment of a large population of patients for whomflow-diverter therapy has not been previously possible. Such patientsare those who have previously suffered from a hemorrhagic aneurysm orwho have been diagnosed as being at risk for hemorrhage from an aneurysmor other vascular anatomy such as from the intracranial arterial system.These patients cannot currently be treated with commercially availableflow-diverting stents because those stents are bare metal, braidedstents whose implantation requires the patient to take blood-thinningmedication (typically aspirin and PLAVIX™ (clopidogrel)) for a longperiod of time following implantation. The purpose of the blood-thinningmedication is to counteract the tendency of the bare-metal stent tocause thrombus (blood clots) to form in the patient's vasculature.However, for a patient who has suffered or is at risk of intracranialhemorrhage, taking the blood-thinning medication can cause, or put thepatient at higher risk of, such a hemorrhage. Low-thrombogenicityflow-diverting stents, such as the coated stents disclosed herein, canmake flow-diverter therapy possible for patients who cannot tolerateblood-thinning medication because the reduced thrombogenicity can reduceor eliminate the need for blood thinners.

In order to implant any of the coated stents disclosed herein, the stentcan be mounted in a delivery system. Suitable delivery systems aredisclosed in U.S. patent application Ser. No. 13/692,021, filed Dec. 3,2012, titled METHODS AND APPARATUS FOR LUMINAL STENTING; and in U.S.Pat. No. 8,273,101, issued Sep. 25, 2012, titled SYSTEM AND METHOD FORDELIVERING AND DEPLOYING AN OCCLUDING DEVICE WITHIN A VESSEL. The entirecontents of both of these documents are incorporated by reference hereinand made a part of this specification. In particular, these documents'teachings regarding braided stent delivery systems and methods may beemployed to deliver any of the coated stents disclosed herein in thesame manner, to the same bodily location(s), and using the samecomponents as are disclosed in both incorporated documents.

Generally, as shown in FIG. 20, a delivery system 400 may be used todeliver a stent 402 into a hollow anatomical structure, such as a bloodvessel. The delivery system 400 can include an elongate core assembly404 that supports or contains the stent 402, and both components can beslidably received in a lumen 410 of a microcatheter 412 or otherelongate sheath for delivery to any region to which the distal openingof the microcatheter 412 can be advanced. The core assembly 404 isemployed to advance the stent 402 through the microcatheter 412 and outthe distal end of the microcatheter 412 so that the stent 402 is allowedto self-expand into place in the blood vessel, across an aneurysm orother treatment location. The core assembly 404 can comprise a wire(e.g. a guidewire), a tube (e.g. a hypotube such as a spiral-cut orslotted hypotube), or a combination of a wire and a tube. The deliverysystem 400 may employ a polymeric member 420 that engages an inner wallof the tubular body and enables longitudinal force transmission from thecore assembly 404 to the tubular body. Such a polymeric member can bemounted on the wire and/or tube.

A treatment procedure can begin with obtaining percutaneous access tothe patient's arterial system, typically via a major blood vessel in aleg or arm. A guidewire can be placed through the percutaneous accesspoint and advanced to the treatment location, which can be in anintracranial artery. The microcatheter is then advanced over theguidewire to the treatment location and situated so that a distal openend of the guidewire is adjacent to the treatment location. Theguidewire can then be withdrawn from the microcatheter and the coreassembly, together with the stent mounted thereon or supported thereby,can be advanced through the microcatheter and out the distal endthereof. The stent can then self-expand into apposition with the innerwall of the blood vessel. Where an aneurysm is being treated, the stentis placed across the neck of the aneurysm so that a sidewall of thestent (e.g. a section of the braided tube) separates the interior of theaneurysm from the lumen of the parent artery. Once the stent has beenplaced, the core assembly and microcatheter are removed from thepatient. The stent sidewall can now perform a flow-diverting function onthe aneurysm, thrombosing the blood in the aneurysm and leading tohealing of the aneurysm.

Because of the low-thrombogenic properties of the coated stentsdisclosed herein, certain additional aspects of the methods of treatmentare possible. For example, the patient can be one who has previouslysuffered from, or who has been diagnosed as being at risk, of hemorrhagefrom an aneurysm or other arterial anatomy such as the intracranialarterial system. The patient can be prescribed a reduced regimen ofblood-thinning medication as compared to the regimen that would benecessary for patient who received an otherwise similar but uncoatedflow-diverting stent. The regimen can be “reduced” in the sense that thepatient takes a lower dosage, fewer medications, less powerfulmedications, follows a lower dosage frequency, and/or takes medicationfor a shorter period of time following implantation of the stent, orotherwise. Alternatively, the patient may be prescribed no bloodthinning medication at all.

The devices and methods discussed herein are not limited to the coatingof stents, but may include any number of other implantable devices.Treatment sites may include blood vessels and areas or regions of thebody such as organ bodies.

Although the detailed description contains many specifics, these shouldnot be construed as limiting the scope of the subject technology butmerely as illustrating different examples and aspects of the subjecttechnology. It should be appreciated that the scope of the subjecttechnology includes other embodiments not discussed in detail above.Various other modifications, changes and variations may be made in thearrangement, operation and details of the method and apparatus of thesubject technology disclosed herein without departing from the scope ofthe present disclosure. Unless otherwise expressed, reference to anelement in the singular is not intended to mean “one and only one”unless explicitly stated, but rather is meant to mean “one or more.” Inaddition, it is not necessary for a device or method to address everyproblem that is solvable by different embodiments of the disclosure inorder to be encompassed within the scope of the disclosure.

What is claimed is:
 1. A medical device for treating an aneurysm, comprising: a tubular member comprising a plurality of braided filaments that form a sidewall and a plurality of pores in the sidewall that are sized to inhibit flow of blood through the sidewall into an aneurysm to a degree sufficient to lead to thrombosis and healing of the aneurysm when the tubular member is positioned in a blood vessel and adjacent to the aneurysm, each of the filaments crossing another of the filaments at a respective crossing point; and an antithrombogenic material distributed over the tubular member such that the pores are substantially free of webs formed by the material such that webs are present at fewer than 5% of the crossing points; wherein the tubular member exhibits an elapsed time before peak thrombin formation that is at least 1.5 times the elapsed time of an identical, uncoated tubular member.
 2. The medical device of claim 1, wherein the pores have an average pore size that is less than or equal to about 500 microns when the member is in an expanded state.
 3. The medical device of claim 1, wherein the pores have an average pore size that is less than or equal to about 320 microns when the member is in an expanded state.
 4. The medical device of claim 3, wherein the pores have an average pore size that is measured using an inscribed circle diameter.
 5. The medical device of claim 1, wherein the distribution of the antithrombogenic material is substantially complete over the tubular member.
 6. The medical device of claim 5, wherein the anti thrombogenic material is generally uniform over the tubular member.
 7. The medical device of any claim 1, wherein the distribution of the antithrombogenic material is substantially complete over at least a circumferential section of the tubular member that is 5 mm or more in length.
 8. The medical device of claim 7, wherein the anti thrombogenic material comprises an antithrombogenic polymer.
 9. The medical device of claim 8, wherein the anti thrombogenic polymer comprises MPC.
 10. The medical device of claim 1, wherein the tubular member comprises a heat-set metallic braid.
 11. The medical device of claim 1, wherein the tubular member is self-expanding.
 12. The medical device of claim 1, wherein the tubular member has an open proximal end, an open distal end, and forms a lumen extending from the proximal end to the distal end.
 13. The medical device of claim 1, wherein the tubular member exhibits an elapsed time before peak thrombin formation that is at least 2.5 times the elapsed time of an identical, uncoated tubular member.
 14. The medical device of claim 1, wherein the tubular member has an expanded diameter, and an unexpanded diameter smaller than the expanded diameter, and the unexpanded diameter is 5 mm or less.
 15. The medical device of claim 14, wherein the unexpanded diameter is 3 mm or less.
 16. A delivery system for treating an aneurysm, the system comprising: an elongate core assembly comprising a tube, a wire, or a combination of a tube and a wire; and the medical device of claim 1 engaged with the core assembly so as to be movable via the core assembly.
 17. The delivery system of claim 16, further comprising a microcatheter configured to be implanted into a blood vessel, wherein the core assembly is configured to extend within the microcatheter.
 18. The delivery system of claim 16, further comprising a polymeric member that engages an inner wall of the tubular member and enables longitudinal force transmission from the core assembly to the tubular member.
 19. A medical device for treating an aneurysm, comprising: a tubular body configured to be implanted in a blood vessel and comprising a plurality of braided filaments, each of the filaments crossing another of the filaments at a respective crossing point, the body being expandable to an expanded state for treatment of the aneurysm, the body having a first section for spanning a neck of the aneurysm and a plurality of pores located between the filaments, the pores in the first section having a first average pore size of less than about 500 microns when the body is in the expanded state; the first section having a substantially complete distribution of an antithrombogenic material over the filaments; wherein the first section is substantially free of webs formed by the antithrombogenic material such that webs are present at fewer than 5% of the crossing points; wherein the tubular body exhibits an elapsed time before peak thrombin formation that is at least 1.5 times the elapsed time of an identical, uncoated tubular body.
 20. The medical device of claim 19, wherein the first average pore size is less than or equal to about 320 microns when the body is in the expanded state.
 21. The medical device of claim 19, wherein the first average pore size is measured using an inscribed circle diameter.
 22. The medical device of claim 19, wherein the first average pore size is the average size of the pores in the first section without the antithrombogenic material.
 23. The medical device of claim 19, wherein the first section comprises less than an entire length of the tubular body.
 24. The medical device of claim 19, wherein the anti thrombogenic material on the first section is generally uniform over the filaments.
 25. The medical device of claim 19, wherein the anti thrombogenic material comprises an antithrombogenic polymer.
 26. The medical device of claim 25, wherein the anti thrombogenic polymer comprises MPC.
 27. The medical device of claim 19, wherein the tubular body comprises a heat-set metallic braid.
 28. The medical device of claim 19, wherein the tubular body is self-expanding.
 29. The medical device of claim 19, wherein the tubular body has an open proximal end, an open distal end, and forms a lumen extending from the proximal end to the distal end.
 30. The medical device of claim 19, wherein the tubular body exhibits an elapsed time before peak thrombin formation that is at least 2.5 times the elapsed time of an identical, uncoated tubular body.
 31. The medical device of claim 19, wherein the tubular body has an expanded diameter, and an unexpanded diameter smaller than the expanded diameter, and the unexpanded diameter is 5 mm or less.
 32. The medical device of claim 31, wherein the unexpanded diameter is 3 mm or less.
 33. A delivery system for treating an aneurysm, the system comprising: an elongate core assembly comprising a tube, a wire, or a combination of a tube and a wire; and the medical device of claim 19 engaged with the core assembly so as to be movable via the core assembly.
 34. The delivery system of claim 33, further comprising a microcatheter configured to be implanted into a blood vessel, wherein the core assembly is configured to extend within the microcatheter.
 35. The delivery system of claim 33, further comprising a polymeric member that engages an inner wall of the tubular body and enables longitudinal force transmission from the core assembly to the tubular body. 